Geniş Bir Türk Kohortundaki Gastrik Adenokarsinomlarda Claudin 18.2 Ekspresyonu

Year 2023, , 122 - 130, 31.08.2023

Aynur Işık , Güneş Güner , Can Zeyneloğlu , Seçil Demirkol Canlı , Hakki Tastan , Aytekin Akyol

https://doi.org/10.47493/abantmedj.1313791

Abstract

Amaç: Claudin 18.2 (CLDN18.2) özellikle gastrik adenokarsinomlarda (GC) eksprese edilen bir sıkı bağlantı proteinidir. CLDN18.2 ekspresyonunun prognostik ve klinikopatolojik etkileri halen bilinmemektedir. CLDN18.2'yi hedef alan Zolbetuximab monoklonal antikoru, ileri evre gastrik adenokarsinomlar için potansiyel bir tedavi olarak değerlendirilmektedir. Bu çalışmada, gastrik adenokarsinomlarda CLDN18.2 ekspresyonunun prognoz ve tümör özelliklerini geniş bir Türk kohortunda araştırmayı amaçladık.
Metot: 263 GC vakası içeren yedi tane doku mikro dizini (TMA) hazırlanmıştır.CLDN18.2 ekspresyonu immünohistokimyal boyama yöntemi ile tespit edilmiş. Vakalar negatif ve pozitif olarak skorlanmıştır.
Bulgular: GC’lerin %14,3'ü (37/258) anti-CLDN18.2 antikoru ile boyanmıştır. Tüm vakaların %7,8'i (20/258) pozitif, %92,2'si (238/258) negatif olarak değerlendirilmiştir. İki grup arasında yaş veya cinsiyet, tümör derecesi, TNM evresi, histolojik alt tip veya genel sağkalım gibi hasta özellikleri açısından istatistiksel olarak anlamlı bir fark bulunamamıştır.
Sonuç: CLDN18.2 ekspresyonu Türk kohortundaki GC’li vakalarda prognoz ile ilişkili değildir. Bununla birlikte CLDN18.2 potansiyel bir terapötik hedeftir ve CLDN18.2 ekspresyonu ile ilgili bilgiler hastalık yönetiminde önemli olacaktır. GC’lerde CLDN18.2 ekspresyonunun klinikopatolojik özellikler üzerindeki etkilerini anlamak için daha fazla çalışmaya ihtiyaç vardır.

Keywords

Gastrik kanser, CLDN18.2, biomarker

Supporting Institution

Yok

Project Number

Yok

Claudin 18.2 Expression in Gastric Adenocarcinomas in a Large Turkish Cohort

Abstract

Background: Claudin 18.2 (CLDN18.2) is a tight junction protein expressed especially in gastric adenocarcinomas. The prognostic and clinicopathologic implications of CLDN18.2 expression is currently unknown. Zolbetuximab monoclonal antibody against CLDN18.2 is under investigation as a potential treatment for advanced gastric cancer (GC). We aimed to investigate the impact of CLDN18.2 expression in GC on prognosis and tumor features in a large Turkish cohort.
Methods: Seven tissue microarrays (TMAs) containing 263 cases of GC were constructed. Assessment of CLDN18.2 expression was performed by immunohistochemistry, where it was scored as negative and positive.
Results: 14.3% (37/258) of GCs were stained with anti-CLDN18.2 antibody. While 7.8% (20/258) of all cases were positive, 92.2% (238/258) were scored as negative. There was no statistically significant difference between the two groups in terms of patient features such as age or sex, tumor grade, TNM stage, histologic subtype or overall survival.
Conclusion: CLDN18.2 expression was not associated with patient prognosis in the Turkish cohort. However, as this molecule is a potential therapeutic target, information about the impact of CLDN18.2 expression will be important in managing patients, therefore more studies are needed to learn more on the outcomes of CLDN18.2 expression on clinicopathologic features in GC.

Keywords

Gastric cancer, CLDN18.2, biomarker

Project Number

Yok

References

• Collaborators GBDSC. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):42-54.
• Li K, Zhang A, Li X, et al. Advances in clinical immunotherapy for gastric cancer. Biochim Biophys Acta Rev Cancer. 2021;1876(2):188615.
• Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-97.
• Javle M, Smyth EC, Chau I. Ramucirumab: successfully targeting angiogenesis in gastric cancer. Clin Cancer Res. 2014;20(23):5875-81.
• Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390(10111):2461-71.
• Shitara K, Kawazoe A, Hirakawa A, et al. Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma. Cancer Sci. 2022.
• Kyuno D, Takasawa A, Takasawa K, Ono Y, et al. Claudin-18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials. Tissue Barriers. 2021:1967080.
• Tureci O, Koslowski M, Helftenbein G, et al. Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals. Gene. 2011;481(2):83-92.
• Sahin U, Tureci O, Manikhas G, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021;32(5):609-19.
• Rohde C, Yamaguchi R, Mukhina S, et al. Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol. 2019;49(9):870-6.
• Xu B, Liu F, Liu Q, et al. Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC). J Gastrointest Oncol. 2020;11(6):1431-9.
• Pellino A, Brignola S, Riello E, et al. Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas. J Pers Med. 2021;11(11).
• Baek JH, Park DJ, Kim GY, et al. Clinical Implications of Claudin18.2 Expression in Patients With Gastric Cancer. Anticancer Res. 2019;39(12):6973-9.
• Dottermusch M, Kruger S, Behrens HM, et al. Expression of the potential therapeutic target claudin-18.2 is frequently decreased in gastric cancer: results from a large Caucasian cohort study. Virchows Arch. 2019;475(5):563-71.
• Arnold A, Daum S, von Winterfeld M, et al. Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas. Clin Transl Oncol. 2020;22(12):2357-63.
• Hong JY, An JY, Lee J, et al. Claudin 18.2 expression in various tumor types and its role as a potential target in advanced gastric cancer. Transl Cancer Res. 2020;9(5):3367-74.
• Ungureanu BS, Lungulescu CV, Pirici D, et al. Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis. Front Oncol. 2021; 11:643872.
• Wang CC, Yeh HY, Popov AN, et al. Genomic insights into the formation of human populations in East Asia. Nature. 2021;591(7850):413-9.
• Kayikcioglu E, Yuceer RO, Cetin B, et al. Prognostic value of claudin 18.2 expression in gastric adenocarcinoma. World J Gastrointest Oncol. 2023;15(2):343-51.
• Matsuda Y, Semba S, Ueda J, et al. Gastric and intestinal claudin expression at the invasive front of gastric carcinoma. Cancer Sci. 2007;98(7):1014-9.